Orbital Complications of Chronic Rhinosinusitis: Two Years' Experience in a Tertiary Referral Hospital.

PURPOSE: To investigate the different clinical manifestations in Egyptian patients with orbital complications of rhinosinusitis (RS) according to the pathology within the paranasal sinuses. METHODS: The medical records of patients presented with chronic RS between August 2018 and December 2020 were retrospectively reviewed. RESULTS: This study included 64 patients: 28 patients with subperiosteal abscess (SPA), 10 with allergic fungal RS, 6 with isolated fungal RS, 6 with invasive fungal RS, and 14 with mucocele. The most common manifestation was proptosis, limitation of ocular motility, periorbital swelling, and pain. A relative afferent pupillary defect was present in all cases of invasive fungal sinusitis. Surgical interventions were performed in 63 out of 64 cases. All the ophthalmological manifestations were reversible except for patients with invasive fungal rhinosinusitis. CONCLUSION: Orbital complications of RS may require early surgical intervention with multidisciplinary counseling between ophthalmologists, otorhinolaryngologists, radiologists, and neurologists.

Equine sinusitis aetiology is linked to sinus microbiome by amplicon sequencing.

BACKGROUND: Information regarding the microbiome in sinusitis using genetic sequencing is lacking and more-in-depth understanding of the microbiome could improve antimicrobial selection and treatment outcomes for cases of primary sinusitis. OBJECTIVES: To describe sinus microbiota in samples from horses with sinusitis and compare microbiota and the presence of antimicrobial resistance genes between primary, dental-related and other secondary causes of sinusitis. STUDY DESIGN: Retrospective case series. METHODS: Records of equine sinusitis from 2017 to 2021 were reviewed and historical microbial amplicon sequence data were obtained from clinical diagnostic testing of sinus secretions. Following bioinformatic processing of bacterial and fungal sequence data, the sinus microbiota and importance of sinusitis aetiology among other factors were investigated from the perspectives of alpha diversity (e.g., number of operational taxonomic units [OTUs], Hill1 Diversity), beta diversity, and differentially abundant taxa. Quantitative PCR allowed for comparisons of estimated bacterial abundance and detection rate of common antibiotic resistance-associated genes. In a smaller subset, longitudinal analysis was performed to evaluate similarity in samples over time. RESULTS: Of 81 samples analysed from 70 horses, the bacterial microbiome was characterised in 66, and fungal in five. Only sinusitis aetiology was shown to significantly influence microbiome diversity and composition (p < 0.05). Dental-related sinusitis (n = 44) was associated with a significantly higher proportion of obligate anaerobic bacteria, whereas primary sinusitis (n = 12) and other (n = 10) groups were associated with fewer bacteria and higher proportions of facultative anaerobic and aerobic genera. Antimicrobial resistance genes and fungal components were exclusively identified in dental-related sinusitis. MAIN LIMITATIONS: Retrospective nature, incomplete prior antimicrobial administration data. CONCLUSIONS: Molecular characterisation in sinusitis identifies microbial species which may be difficult to isolate via culture, and microbiome profiling can differentiate sinusitis aetiology, which may inform further treatment, including antimicrobial therapy.

Molecular analysis of dominant paranasal sinus bacteria in patients with and without chronic rhinosinusitis.

Recent studies have established the possible role of microbiota in developing various diseases. In this regard, attention has shifted to the evaluation of microbiota changes in the paranasal sinuses and its relationship to chronic rhinosinusitis (CRS), especially CRS with nasal polyposis (CRSwNP). This study aimed to examine the bacterial communities of the sphenoidal sinus in Iranian patients with and without CRS. The investigation included 36 subjects, including 18 patients with CRSwNP who underwent Functional Endoscopic Sinus Surgery (FESS) and 18 non-CRS patients who underwent Endoscopic Endonasal Approach (EEA) for pituitary adenoma. The surgeries were performed under general anesthesia, and the sphenoidal sinus was sampled using sterile rayon-tipped swabs coated with a sheet. TaqMan quantitative real-time polymerase chain reaction (qPCR) method (the 16S rDNA gene from bacteria) was used for detection of bacterial communities in different samples. Staphylococcus haemolyticus and Pseudomonas aeruginosa were significantly more prevalent in CRS patients than non-CRS patients (P value ≤ 0.05). However, no significant difference in the frequency of Corynebacterium spp. and Staphylococcus aureus was observed between the two groups, and no Streptococcus pneumoniae or Haemophilus influenza species were isolated from any of the samples. The current study's findings indicated a significant difference in the frequency of certain bacterial species in patients with CRS vs. non-CRS patients. By establishing a link between microbial burden and CRS, it is possible to develop effective treatments or even prevent disorders in this body area.

Chitogel following endoscopic sinus surgery promotes a healthy microbiome and reduces postoperative infections.

BACKGROUND: Postoperative infections following endoscopic sinus surgery (ESS) impair wound healing and lead to poor outcomes. The aim of this study is to assess the effectiveness of Chitogel to reduce postoperative infections and restore a healthy microbiome following ESS. METHODS: In this double-blinded randomized control trial, 25 patients undergoing ESS were prospectively recruited. At the end of surgery, patients were randomized to receive Chitogel to one side of the sinuses (allowing the other side to serve as control). Patients underwent routine follow-up with nasoendoscopies performed at 2, 6, and 12 weeks postoperatively. Sinus ostial measurements, microbiology, and microbiome swabs from bilateral sides were collected intraoperatively and at 12 weeks postoperatively. Additional swabs were collected if infection was present. RESULTS: Improved endoscopic appearance of the sinuses (p = 0.03) and ostial patency were noted on the Chitogel side compared with control at 12 weeks (p < 0.001). A significant decrease in infections on the Chitogel side (12.0%) compared with control (52.0%) (p = 0.005) was evident. Following the use of Chitogel, there was a significant increase in the combined relative abundance of commensals Corynebacterium and Cutibacterium (Propionibacterium) from 30.15% at baseline to 46.62% at 12 weeks compared with control (47.18% to 40.79%) (p.adj = 0.01). CONCLUSION: Chitogel significantly improved both the nasoendoscopic appearance of the sinuses and sinus ostial patency at 12 weeks postoperatively. Chitogel used following ESS helps restore an improved microbiome resulting in an increase in the relative abundance of commensals Corynebacterium and Cutibacterium (Propionibacterium). A significant decrease in postoperative infections was noted following use of Chitogel.

Nasal microbiome in chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is defined as an inflammatory disorder of the paranasal sinuses and of the nasal mucosa that lasts 12 weeks or longer. In CRS microbes contribute to the disease pathogenesis. Clinical microbiology is focused on finding single pathogens that causes the disease and the main goal is the use of antibiotics to kill bacteria. Efforts to achieve a better understanding of CRS include the study of the sinus microbiome, and to evaluate the ability of probiotics to augment homeostasis and modulate the immune response of the host mucosa. This review provides an update on the role of the microbiome in CRS. The study was conducted using two databases: PubMed and Science Direct. We searched for articles in English that matched the review topic. We first used the abstracts of articles to assess whether they met the inclusion criteria. We also reviewed the references of the selected articles and read those with titles that might be of interest. Several studies have shown that endogenous microbiome dysbiosis can impact mucosa health and disease severity. Some bacterial species presenting protective or pathogenic effect. Antimicrobial agents can create a similar disruption and impact the nasal microbiome balance. On the other hand, probiotics offers a promising avenue for developing systemic and topical therapies geared towards strategic manipulation of the biological host load, thereby augmenting immune homeostasis. A better comprehension of sinus-nasal microbiome in healthy and in CRS patients and the link with different CRS phenotype can help in developing new prognostics, diagnostics, and therapeutics strategies. Going forward, the use of probiotics can restore the native sinus ecology with significant therapeutic and preventive implications.

Adaptation and genomic erosion in fragmented Pseudomonas aeruginosa populations in the sinuses of people with cystic fibrosis.

Pseudomonas aeruginosa notoriously adapts to the airways of people with cystic fibrosis (CF), yet how infection-site biogeography and associated evolutionary processes vary as lifelong infections progress remains unclear. Here we test the hypothesis that early adaptations promoting aggregation influence evolutionary-genetic trajectories by examining longitudinal P. aeruginosa from the sinuses of six adults with CF. Highly host-adapted lineages harbored mutator genotypes displaying signatures of early genome degradation associated with recent host restriction. Using an advanced imaging technique (MiPACT-HCR [microbial identification after passive clarity technique]), we find population structure tracks with genome degradation, with the most host-adapted, genome-degraded P. aeruginosa (the mutators) residing in small, sparse aggregates. We propose that following initial adaptive evolution in larger populations under strong selection for aggregation, P. aeruginosa persists in small, fragmented populations that experience stronger effects of genetic drift. These conditions enrich for mutators and promote degenerative genome evolution. Our findings underscore the importance of infection-site biogeography to pathogen evolution.

CT and MRI Findings of Invasive Mucormycosis in the Setting of COVID-19: Experience From a Single Center in India.

An increasing incidence of rhinoorbitocerebral mucormycosis (ROCM) among patients with COVID-19 has recently been reported in India. We report the imaging findings for 25 patients with COVID-19 and invasive ROCM at a single hospital in India. Findings included sinus wall erosions (n = 20), air within bony sinus structures (n = 11), and focal mucosal nonenhancement (n = 8). Orbital, vascular, and intracranial complications were also observed. Radiologists should recognize the increasing incidence of ROCM among patients with COVID-19 to facilitate early diagnosis.

Longitudinal analysis of sinus microbiota post endoscopic surgery in patients with cystic fibrosis and chronic rhinosinusitis: a pilot study.

BACKGROUND: Cystic fibrosis is a debilitating, autosomal recessive disease which results in chronic upper and lower airway infection and inflammation. In this study, four adult patients presenting with cystic fibrosis and chronic rhinosinusitis were recruited. Culture and molecular techniques were employed to evaluate changes in microbial profiles, host gene expression and antimicrobial resistance (AMR) in the upper respiratory tract over time. METHODS: Swab samples from the sinonasal cavity were collected at the time of surgery and at follow-up clinics at regular time intervals for up to 18 months. Nucleic acids were extracted, and DNA amplicon sequencing was applied to describe bacterial and fungal composition. In parallel, RNA was used to evaluate the expression of 17 AMR genes and two inflammatory markers (interleukins 6 and 8) using custom qPCR array cards. Molecular results were compared with routine sinus and sputum culture reports within each patient. RESULTS: Bacterial amplicon sequencing and swab culture reports from the sinonasal cavity were mostly congruent and relatively stable for each patient across time. The predominant species detected in patients P02 and P04 were Pseudomonas aeruginosa, Staphylococcus aureus in patient P03, and a mixture of Enterobacter and S. aureus in patient P01. Fungal profiles were variable and less subject specific than bacterial communities. Increased expressions of interleukins 6 and 8 were observed in all patients throughout the sampling period compared with other measured genes. The most prevalent AMR gene detected was ampC. However, the prevalence of AMR gene expression was low in all patient samples across varying time-points. CONCLUSIONS: We observed a surprising degree of stability of sinonasal microbial composition, and inflammatory and AMR gene expression across all patients post sinus surgery.

Post coronavirus disease mucormycosis: a deadly addition to the pandemic spectrum.

OBJECTIVE: To study the possible association between invasive fungal sinusitis (mucormycosis) and coronavirus disease. METHODS: A prospective observational study was conducted at a tertiary care centre over four months, involving all patients with mucormycosis of the paranasal sinuses suffering from or having a history of coronavirus disease infection. RESULTS: Twenty-three patients presented with mucormycosis, all had an association with coronavirus disease 2019. The ethmoids (100 per cent) were the most common sinuses affected. Intra-orbital extension was seen in 43.47 per cent of cases, while intracranial extension was only seen in 8.69 per cent. Diabetes mellitus was present in 21 of 23 cases, and was uncontrolled in 12 cases. All patients had a history of steroid use during their coronavirus treatment. CONCLUSION: New manifestations of coronavirus disease 2019 are appearing over time. The association between coronavirus and mucormycosis of the paranasal sinuses must be given serious consideration. Uncontrolled diabetes and over-zealous use of steroids are two main factors aggravating the illness, and both of these must be properly checked.

The influence of nasal microbiome diversity and inflammatory patterns on the prognosis of nasal polyps.

To understand the inflammatory microenvironment and microbiome factors for prognosis of chronic rhinosinusitis with polyps (CRSwNP), we explored the difference in characteristics of the microbiome of the nasal sinuses and inflammatory cytokines between recurrent and non-recurrent groups. We collected nasal secretions and polyp tissue from 77 CRSwNP patients. Then, we extracted microbial DNA from cotton swabs, performed high-throughput sequencing based on 16S rRNA to detect bacterial community composition, and analyzed cytokines such as IL-5, IL-8, IL-17a, IL-17e, IL-18, IL-27 and INF-gamma from polyp tissue using Luminex. The eosinophil and neutrophil cells in the peripheral blood and polyp tissue were counted. Postoperative follow-up of patients with CRSwNP for 1 year was conducted to record the recurrence of nasal polyps and analyze the correlation between the recurrence of nasal polyps and the characteristics of inflammatory cytokines, inflammatory cell count and nasal microbial diversity. After 1 year of follow-up, there were 12 recurrent patients, including 5 males and 7 females. Postoperative recurrence of nasal polyps was not significantly correlated with age, sex, asthma, allergic rhinitis or other allergic diseases in CRSwNP patients. In terms of the total nasal symptom score, the recurrent group was significantly higher than the non-recurrent group. In nasal polyp tissues, eosinophils (40.83/HP) and neutrophils (30.83/HP) in patients with CRSwNP in the recurrent group were significantly higher than those in the non-recurrent group (13.72/HP), and neutrophils (18.5/HP) were also significantly higher in the recurrent group than the non-recurrent group. The expression levels of IFN-, IL-17A, IL-17E and IL-18 were significantly higher in the recurrent group than in the non-recurrent group, and the positive rates were not different. In Southwest China, Enterobacteria and anaerobic bacteria may be correlated with the inflammatory pattern expression of nasal polyps. The neutrophil-mediated inflammatory response plays an important role in patients with CRSwNP in Southwest China and is correlated with nasal polyp recurrence. Recurrence of nasal polyps after endoscopic sinus surgery may be potentially associated with a reduced abundance of protective microorganisms and an increased number of pathogenic microorganisms.

Loss of bacterial diversity in the sinuses is associated with lower smell discrimination scores.

Olfactory impairment affects ~ 20% of the population and has been linked to various serious disorders. Microbes in the nasal cavity play a key role in priming the physiology of the olfactory epithelium and maintaining a normal sense of smell by the host. The aim of this study was to explore the link between olfactory dysfunction and nasal bacterial communities. A total of 162 subjects were recruited for this study from a specialized olfactory dysfunction clinic and placed into one of three groups: anosmia, hyposmia or normosmia. Swabs from the nasal middle meatus were collected from each subject then processed for bacterial 16S rRNA gene sequencing. No overall differences in bacterial diversity or composition were observed between the three cohorts in this study. However, the relative abundances of Corynebacterium spp. and Streptococcus spp. were significantly (p < 0.05) different in subjects with olfactory loss. Furthermore, subjects with deficiencies in discriminating between smells (based on discrimination scores) had a lower bacterial diversity (Simpson's evenness p < 0.05). While these results are preliminary in nature, potential bacterial biomarkers for olfactory loss were identified. These findings need to be further validated and biologically tested in animal models.

Cerebrospinal fluid leak from lateral orbit during exenteration for mucormycosis.

We describe an elderly diabetic patient presenting with sudden onset right-sided proptosis and vision loss secondary to rhino-orbital mucormycosis and central retinal vascular occlusion. He underwent orbital exenteration that was complicated by intraoperative cerebrospinal fluid (CSF) leak from lateral orbital wall. The leak was surgically repaired and the patient recovered well. We postulate the cause of the CSF leak to be twofold: necrotic periorbital tissue due to mucormycosis rendering the thin bones susceptible to damage and second, intraoperative manipulation and dissection at the orbital apex with monopolar cautery and instruments. We describe measures taken to successfully repair the CSF leak and the possible precautions that can be taken to avoid it.

The Microbiome and Chronic Rhinosinusitis.

Chronic rhinosinusitis (CRS) is persistent inflammation and/or infection of the nasal cavity and paranasal sinuses. Recent advancements in culture-independent molecular techniques have enhanced understanding of interactions between sinus microbiota and upper airway microenvironment. The dysbiosis hypothesis-alteration of microbiota associated with perturbation of the local ecological landscape-is suggested as a mechanism involved in CRS pathogenesis. This review discusses the complex role of the microbiota in health and in CRS and considerations in sinus microbiome investigation, dysbiosis of sinus microbiota in CRS, microbial interactions in CRS, and development of preclinical models. The authors conclude with future directions for CRS-associated microbiome research.

Antibodies against the DNABII protein integration host factor (IHF) inhibit sinus implant biofilms.

OBJECTIVES: Chronic rhinosinusitis is a common, costly condition often treated with endoscopic sinus surgery and intraoperative placement of intranasal sinus implant materials. Whereas these materials aid in postoperative healing, they also support bacterial biofilm formation and thus contribute to negative outcomes. This study examined pretreatment of sinus implant materials with antibody against an essential bacterial biofilm structural component, the DNABII family of DNA-binding proteins, as a strategy to prevent biofilm formation. METHODS: Sinus implant materials were equilibrated in immunoglobulin G (IgG)-enriched antiserum against the DNABII protein integration host factor (IHF), individually or in combination with amoxicillin-clavulanate prior to inoculation with nontypeable Haemophilus influenzae (NTHI), a predominant pathogen of chronic rhinosinusitis. After 16 hours, the bacterial burden was quantitated and compared to pretreatment with saline, IgG-enriched naive serum, or amoxicillin-clavulanate alone. RESULTS: NTHI readily formed biofilms on all three materials in vitro. However, pretreatment of each material with IgG-enriched anti-IHF resulted in a significant decrease in bacterial burden compared to controls (P ≤ 0.05). Moreover, a significant and synergistic outcome was achieved with a cocktail of anti-IHF plus amoxicillin-clavulanate (P ≤ 0.05) with complete inhibition of NTHI biofilm formation on all three materials. CONCLUSIONS: Biofilm formation was well supported in vitro on three sinus implant materials that vary in composition and resorption characteristics; however, pretreatment of each with DNABII protein targeted antibodies in combination with a previously ineffective antibiotic was highly effective to prevent the formation NTHI biofilms. These data demonstrate the potential for clinical utility of pretreatment of sinus implant and additional surgical materials with anti-DNABII antibodies. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1364-1371, 2020.

Clinicopathologic characteristics of paranasal sinus fungus ball: retrospective, multicenter study in Korea.

PURPOSE: Fungus ball (FB) is the most common type of fungal rhinosinusitis and the prevalence of FB has increased over the past 10 years. The aim of this study was to compare the clinical characteristics of Korean adult patients with FB and chronic rhinosinusitis (CRS) without FB. METHODS: We retrospectively analyzed data on 1362 patients (147 FB and 1215 CRS) who underwent endoscopic sinus surgery at nine Korean medical centers in 2005, 2010, and 2016. We evaluated the prevalence of FB and compared the clinical characteristics of FB and CRS. Medical records, computed tomography (CT) findings, atopic status, concomitant diseases, tissue, and blood eosinophil count were assessed. RESULTS: The prevalence of FB was significantly higher in 2016 (15.9%) than in the other years (7.8% in 2005 and 7.5% in 2010). The FB patients were more likely to be female, older, have unilateral disease and less likely to have allergy compared to the CRS patients. The most common main complaint related to CRS and FB was nasal obstruction. CT determined that unilateral disease and maxillary sinus dominancy were common in patients with FB. The incidence of concomitant diseases was much higher in FB, with lower tissue and blood eosinophilia. CONCLUSION: FB is commonly encountered in older women with the increased prevalence. FB had a different clinical presentation, radiological findings, and prognosis than CRS. Further studies are needed to understand the pathophysiologic mechanisms underlying the development of FB.

Anterior Nares Diversity and Pathobionts Represent Sinus Microbiome in Chronic Rhinosinusitis.

It is generally believed that the microbiome plays a role in the pathophysiology of chronic rhinosinusitis (CRS), though its exact contribution to disease development and severity remains unclear. Here, samples were collected from the anterior nares, nasopharynx, and maxillary and ethmoid sinuses of 190 CRS patients and from the anterior nares and nasopharynx of 100 controls. Microbial communities were analyzed by Illumina sequencing of the V4 region of 16S rRNA. The phenotype and patient characteristics were documented, and several serum inflammatory markers were measured. Our data indicate a rather strong continuity for the microbiome in the different upper respiratory tract (URT) niches in CRS patients, with the microbiome in the anterior nares being most similar to the sinus microbiome. Bacterial diversity was reduced in CRS patients without nasal polyps compared to that in the controls but not in CRS patients with nasal polyps. Statistically significant differences in the presence/absence or relative abundance of several taxa were found between the CRS patients and the healthy controls. Of these, Dolosigranulum pigrum was clearly more associated with URT samples from healthy subjects, while the Corynebacterium tuberculostearicum, Haemophilus influenzae/H. aegyptius, and Staphylococcus taxa were found to be potential pathobionts in CRS patients. However, CRS versus health as a predictor explained only 1 to 2% of the variance in the microbiome profiles in an adonis model. A history of functional endoscopic sinus surgery, age, and sex also showed a minor association. This study thus indicates that functional studies on the potential beneficial versus pathogenic activity of the different indicator taxa found here are needed to further understand the pathology of CRS and its different phenotypes. (This study has been registered at ClinicalTrials.gov under identifier NCT02933983.)IMPORTANCE There is a clear need to better understand the pathology and specific microbiome features in chronic rhinosinusitis patients, but little is known about the bacterial topography and continuity between the different niches of the upper respiratory tract. Our work showed that the anterior nares could be an important reservoir for potential sinus pathobionts. This has implications for the diagnosis, prevention, and treatment of CRS. In addition, we found a potential pathogenic role for the Corynebacterium tuberculostearicum, Haemophilus influenzae/H. aegyptius, and Staphylococcus taxa and a potential beneficial role for Dolosigranulum Finally, a decreased microbiome diversity was observed in patients with chronic rhinosinusitis without nasal polyps compared to that in healthy controls but not in chronic rhinosinusitis patients with nasal polyps. This suggests a potential role for the microbiome in disease development or progression of mainly this phenotype.

Longitudinal study of the bacterial and fungal microbiota in the human sinuses reveals seasonal and annual changes in diversity.

There is a pressing need for longitudinal studies which examine the stability of the sinonasal microbiota. In this study, we investigated bacterial and fungal community composition of the sinuses of four healthy individuals every month for one year, then once every three months for an additional year to capture seasonal variation. Sequencing of bacterial 16S rRNA genes and fungal ITS2 revealed communities that were mainly dominated by members of Actinobacteria and Basidiomycota, respectively. We observed overall shifts in both bacterial and fungal community diversity that were attributable to a combination of individual, seasonal and annual changes. The results suggest that each of the subjects possessed a strong bacterial sinonasal signature, but that fungal communities were less subject specific. Differences in fungal and bacterial diversity between subjects, and which OTUs may be correlated with seasonal differences, were investigated. A small core community that persisted throughout the two year sampling period was identified: Corynebacterium, Propionibacterium and Staphylococcus, and one type of fungus, Malassezia restricta. It is likely that bacterial and fungal airway microbiomes are dynamic and experience natural shifts in diversity with time. The underlying reasons for these shifts appear to be a combination of changes in environmental climate and host factors.